Altered Chemotherapy Sequencing During Neoadjuvant Therapy for Patients With Stage II or III Rectal Adenocarcinoma

Phase 1

Withdrawn

• Conditions: Stage II Rectal Cancer; Stage III Rectal Cancer
• Interventions: Drug: Capecitabine; Drug: 5-FU; Drug: Leucovorin; Drug: Oxaliplatin; Radiation: radiation; Procedure: total mesorectal excision

• Registration Number: NCT01302613
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

The primary objective of the pilot portion of this study is to establish the safety and tolerability of an extended treatment break period in patients who have undergone neoadjuvant chemoradiotherapy as well as use of systemic therapy during this break.

Detailed Description

The proposed protocol aims to continue tumor-directed therapy during the typical "break period" in an effort to improve on both local tumor response as well as distant disease control. First, the duration from completion of chemoradiotherapy would increase from 6-8 weeks to 9-11 weeks. As noted above, this may allow for further cell death with resultant pathologic downstaging. Secondly, the protocol calls for continued systemic therapy during the 9-11 week period, thus allowing continuation of therapies directed towards both the primary as well as distant sites of disease. The primary aim of this pilot study would be to establish the feasibility of this intensified neoadjuvant approach, especially with respect to tolerability of the subsequent pelvic surgery. A subsequent phase II portion will evaluate the efficacy of this treatment approach.

Study Timeline

• Study First Submitted: 2011-02-21
• Study First Submitted QC: 2011-02-23
• Study First Posted: 2011-02-24
• Study Start: 2011-03
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2019-02
• Last Update Submitted: 2020-08-19
• Last Update Posted: 2020-08-20

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Signed study-specific informed consent form
2. Age > 18 years old
3. Zubrod performance status 0-1
4. Biopsy proven primary malignancy
5. AJCC Stage II or III disease (T3-4 and/or N1-2 disease) as determined by endoscopic ultrasound and/or MRI staging
6. Pretreatment rectal endoscopic ultrasound and pelvic MRI, colonoscopy, CT of chest, abdomen, and pelvis, and laboratory values as discussed below

Exclusion Criteria

1. History of inflammatory bowel disease

2. Previous pelvic radiotherapy

3. A major psychiatric illness which would limit understanding of the proposed protocol treatment and consent process.

4. Men and women of reproductive potential must agree to use an effective contraception method

5. Pregnant or lactating women

6. Severe, active co-morbidity, defined as

   • Unstable angina and/or CHF requiring hospitalization within the last six months
   • Transmural myocardial infarction within the last 6 months
   • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

7. Presence of metastatic disease, including liver metastases

8. Laboratory values out of range

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
arm one	radiation	RT + Chemo + surgery
arm one	total mesorectal excision	RT + Chemo + surgery
arm one	Capecitabine	RT + Chemo + surgery
arm one	5-FU	RT + Chemo + surgery
arm one	Leucovorin	RT + Chemo + surgery
arm one	Oxaliplatin	RT + Chemo + surgery

Primary Outcome Measures

Name	Time	Method
The primary study endpoint for the phase I portion of this study is to assess surgical complications through the Clavien grading system.	90 days	The adverse events will be followed prospectively from the date of surgery for 90 days. Dose-limiting toxicity (DLT) will be defined as \> grade 3 anastomotic stricture or leak, infection (including pelvic abscess or wound infection), small bowel obstruction, or fistualization. Any other post-operative complication thought related directly to the surgical intervention that is a grade 3 or higher Clavien complication will also be considered dose-limiting toxicity.

Secondary Outcome Measures

Name	Time	Method
The primary endpoint of the phase II portion of the study is complete pathologic response.	9 to 11 weeks	9 to 11 weeks after the completion of the initial chemoradiotherapy.

Trial Locations

Locations (1)

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States